29been reported to engineer nanoparticles and their architectures with desirable size,
shape, and functionality, including those based on the “nano-toolbox”-based pro-
grammable self-assembly approach [ 29 , 36 , 82 – 84 ]. The capability of modulating
the geometric configurations and surface characteristics suggests opportunities to
overcome the hurdle, while considerably increasing blood circulation times as well
as biocompatibility [ 29 , 36 , 82 ].
2.5 Nanoenvironments and Nano-Scaffolds
In living organisms, stem cells are prevented from exiting the mitotic cycle by spe-
cific environments, called niches [ 89 ]. These niches are formed by cellular and non-
cellular elements. The non-cellular elements include instructive extracellular matrix
molecules (e.g., collagen, elastin, proteoglycan, fibronectin, and laminin) secreted
by cells in the vicinity of stem cells. The nanoscale structure of the extracellular
matrix provides cellular anchorage points and presents clues to guide cell behavior.
The ability to engineer materials to resemble the structural complexity of the extra-
cellular matrix, including its nano-textured topography, has made large contribu-
tions to our understanding of several cellular processes including stem cell-matrix
interactions, stem cell differentiation in response to different nanoscale topogra-
phies, and stem cell migration [ 2 ]. Tissue engineered nano-scaffolds can assist in
cell adhesion, engraftment survival, migration, differentiation, and organization.
These nano-scaffolds often containing nanofibers have been shown to improve mes-
enchymal stem cell viability [ 90 ]. One of the ultimate applications of nanofiber-
based scaffolds is in vivo stem cell transplantation, where nano-scaffold would act
as a temporary extracellular matrix to guide tissue formation and typically would
degrade in concert with deposition of new in vivo matrix. Unfortunately, there are
few in vivo studies of stem cells transplanted into these scaffolds [ 91 ]. In contrast to
traditional scaffolds for cell transplantation, nanofiber-based scaffolds offer the
opportunity to control stem cell behavior by incorporation of high-density epitopes
and control of cell alignment. Moreover, the intrinsic properties of the scaffolds
might contribute to the differentiation of endogenous stem cells in the vicinity of the
implant.
In Fig. 2.8 below stem cells or progenitor cells are seeded on three-dimensional
scaffolds formed by nanofibers. These nanofibers may present a high density of
ligands, including cell-adhesion epitopes or immobilized growth factors, for stem
cell differentiation. The tissue constructs can be implanted immediately after incor-
poration of a cell source (<24 h) into the defective tissue. Alternatively, the tissue
constructs can be cultured in bioreactors to allow cell proliferation, differentiation,
and three-dimensional organization before their final implantation. In both cases,
the scaffold acts as a temporary 3D ECM for cell adhesion and tissue formation and
typically is designed to degrade when new extracellular matrix is deposited [ 2 ].
2 Nanotechnology-Based Stem Cell Applications and Imaging